This NIAAA Alcohol Research Center (ARC) is the catalytic element that pulls together a broad group across the University of North Carolina at Chapel Hill, a major research University and Medical Center. ARC leadership stimulates interaction through regular research seminars, annual clinical conferences, core research services and through stimulation and initiation of interests on the effects of alcohol on health. Pilot projects, training programs for students and collaborations bring new investigators into scholarly interactions and interests through the ARC. The ARC synergizes with existing investigator funding to promote interactions of multidisciplinary investigators focused on human clinical trials, human genetics, tissue pathology as well as pathologic behavior and the effects of ethanol on brain and development. This Alcohol Research Center Grant (ARC) is focused on the central theme that alcohol-induced pathology involves a spectrum of molecular and cellular changes that span the progression from initial exposure to alcohol abuse and alcoholism. Interdisciplinary research themes include studies on gene regulation, transcription factor activation, receptor trafficking, kinase signaling, oxidative stress and inflammation. Investigators employ state of the art techniques including confocal microscopy combined with measures of cellular proteins and mRNA to determine mechanisms that underlie behavioral and tissue pathology. This proposal connects 14 currently funded independent projects with additional cores and research components. The pathologies associated with alcoholism represent a central theme that is divided into two foci, tissue pathology and the pathological processes that regulate alcohol seeking behaviors. Alcohol consumption is a component of both of these pathologies and this ARC integrates drinking models that range from moderate levels of voluntary drinking, to early experimentation with ethanol, to heavy drinking and dependence, to high blood ethanol levels that induce brain and fetal damage. This Alcohol Research Center is a research intensive Center with molecular neuroscience linking all components creating a strong overlapping interest in ethanol induced changes in signaling and gene induction mechanisms as well as methodologies and efficient sharing of core facilities. The aims of this ARC are: 1. To investigate molecular mechanisms of alcohol-induced behavioral, tissue, and cellular pathogenesis, and 2) To disseminate educational materials to health professionals and youth. This Alcohol Research Center contributes leadership and scientific strength to basic and clinical research, translates science to health professionals, youth and others and provides a comprehensive Alcohol Research Center for leading activities in North Carolina.